Contemporary Risk Estimates of Three HbA1c Variables for Myocardial Infarction in 101,799 Patients Following Diagnosis of Type 2 Diabetes

Abstract

OBJECTIVEThis study evaluated the risk of myocardial infarction (MI) by impaired glycemic control in a contemporary large cohort of patients with type 2 diabetes followed from diagnosis. RESEARCH DESIGN AND METHODSPatients with type 2 diabetes diagnosed between 1995 and 2011 were retrieved from the Clinical Practice Research Datalink in the U.K., and followed from diagnosis until event of MI or end of study in 2013. Two subcohorts were defined: an early cohort with those diagnosed from 1997 to 2004 and a recent cohort with those diagnosed from 2004 to 2011. Association between each of three HbA 1c metrics and MI was estimated using adjusted proportional hazards models. RESULTSIn the overall cohort (n = 101,799), the risk increase for MI per 1% (10 mmol/mol) increase in HbA 1c was higher for updated latest and updated mean HbA 1c of 1.11 (95% CI 1.09-1.13) and 1.15 (1.13-1.18) than for baseline HbA 1c of 1.05 (1.03-1.06). In the early subcohort, the corresponding risk estimates were greater than those in the recent subcohort. When categorized, the updated latest variable showed an increased risk for HbA 1c <6% (42 mmol/mol), relative category 6-7%, in the recent but not in the early subcohort, with hazard ratios of 1.23 (1.08-1.40) and 1.01 (0.84-1.22), respectively. CONCLUSIONSThe two time-updated HbA 1c variables show a stronger relation with MI than baseline HbA 1c . The risk association between HbA 1c and MI has decreased over time. In recently diagnosed patients with type 2 diabetes, an increased risk of MI exists at a current HbA 1c of <6.0% (42 mmol/mol).The global burden of diabetes has risen dramatically during the last two decades and is expected to affect more than 500 million adults worldwide by 2030, with the majority having type 2 diabetes (1). Patients with type 2 diabetes have a shorter lifeexpectancy, and myocardial infarction (MI) is the most common cause of the excess risk of death in these patients (2-4). Studies of glycemia as a risk factor for cardiovascular events have shown somewhat different results. Three large clinical trials,

Contemporary risk estimates of three HbA1cvariables in relation to heart failure following diagnosis of type 2 diabetes

“…Nonetheless, this is an essential point from our findings since the HRs described by 1% higher HbA 1c differ greatly depending on the HbA 1c metric used. It is noteworthy that in accordance with our recent analysis of HbA 1c in relation to MI (15), there was a J-shaped pattern for the latest HbA 1c variable. Although this finding is repeated here for another CV complication and it could be inferred that very tight glycaemic control, for example, HbA 1c close to normal levels may be harmful, it should be interpreted with caution since patients with HbA 1c <6% (42 mmol/ mol) have a glycaemic control lower than general targets.…”

“…14 Recently, we found that the estimates of glycaemic control in relation to myocardial infarction varied over time with less strong associations during more recent time periods. 15 The most commonly used measure of glycaemia is haemoglobin A 1c (HbA 1c ). 16 However, a deeper understanding of the statistical application of repeated measures of HbA 1c is needed.…”

“…15 17 Most commonly used have been the baseline HbA 1c and the updated mean HbA 1c (which at the time point for each new registration is the mean of all measurements taken thus far). Therefore, following a similar comparative HbA 1c metric approach, 15 we sought in this study to evaluate HbA 1c in relation to HF in a large contemporary population of persons with T2D and compared three distinct methods using HbA 1c measurements from diabetes diagnosis and onwards.…”

Early Glycemic Control and Magnitude of HbA1c Reduction Predict Cardiovascular Events and Mortality: Population-Based Cohort Study of 24,752 Metformin Initiators

“…Although the large clinical randomized controlled trials have failed to show a clear beneficial effect of early intensive glycemic control on cardiovascular events in type 2 diabetes (5), long-term follow-up studies from the UK Prospective Diabetes Study (UKPDS) (8) and Veterans study (9) have suggested a beneficial cardiovascular effect, termed "metabolic memory" or "legacy effect." (10) In observational research, most studies, but not all, suggest that having a low glycemic level measured at some point of time is associated with fewer cardiovascular events and mortality in type 2 diabetes (11)(12)(13)(14)(15)(16)(17)(18). Some studies found a linear relationship between successively lower glycemic levels and fewer cardiovascular events (11,12,18), whereas others reported a J-or U-shaped curve (14)(15)(16).…”

“…(10) In observational research, most studies, but not all, suggest that having a low glycemic level measured at some point of time is associated with fewer cardiovascular events and mortality in type 2 diabetes (11)(12)(13)(14)(15)(16)(17)(18). Some studies found a linear relationship between successively lower glycemic levels and fewer cardiovascular events (11,12,18), whereas others reported a J-or U-shaped curve (14)(15)(16). Comparison of these studies is hampered by inclusion of case patients with prevalent diabetes with different time of diabetes duration and by different ways of measuring glycemic control.…”